Hydrogen Peroxide Radical Damage

Download >>> https://geags.com/2tkYcu

We elucidated the cytoprotective effects of hyperoside (quercetin-3-O-galactoside) against hydrogen peroxide (H2O2)-induced cell damage. We found that hyperoside scavenged the intracellular reactive oxygen species (ROS) detected by fluorescence spectrometry, flow cytometry, and confocal microscopy. In addition, we found that hyperoside scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4)+H2O2) in a cell-free system, which was detected by electron spin resonance (ESR) spectrometry. Hyperoside was found to inhibit H2O2-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. In addition, hyperoside pretreatment inhibited the H2O2-induced activation of caspase-3 measured in terms of levels of cleaved caspase-3. Hyperoside prevented H2O2-induced lipid peroxidation as well as protein carbonyl. In addition, hyperoside prevented the H2O2-induced cellular DNA damage, which was established by comet tail, and phospho histone H2A.X expression. Furthermore, hyperoside increased the catalase and glutathione peroxidase activities. Conversely, the catalase inhibitor abolished the cytoprotective effect of hyperoside from H2O2-induced cell damage. In conclusion, hyperoside was shown to possess cytoprotective properties against oxidative stress by scavenging intracellular ROS and enhancing antioxidant enzyme activity.

There is an increasing evidence that oxidative stress is implicated in the processes of inflammation and carcinogenesis. It has been shown that kahweol and cafestol, coffee-specific diterpenes, exhibit chemoprotective effects. This study investigated the effects of kahweol and cafestol, coffee-specific diterpenes, on the hydrogen peroxide (H(2)O(2))-induced oxidative stress and DNA damage in NIH3T3 cells. When the cells were treated with kahweol or cafestol, cytotoxicity, lipid peroxidation, and reactive oxygen species production induced by H(2)O(2) were markedly reduced in a dose-dependent manner. Moreover, kahweol and cafestol were shown to be highly protected against H(2)O(2)-induced oxidative DNA damage as determined by the Comet (single cell gel electrophoresis) assay and the measurement of 8-oxoguanine content in NIH3T3 cells. Kahweol and cafestol also protected hydroxyl radical-induced 2-deoxy-d-ribose degradation by ferric ion-nitrilotriacetic acid and H(2)O(2). In addition, kahweol and cafestol efficiently removed the superoxide anion generated from the xanthine/xanthine oxidase system. These results suggest that kahweol and cafestol are effective in protecting against H(2)O(2)-induced oxidative stress and DNA damage, probably via scavenging free oxygen radicals, and that kahweol and cafestol act as antioxidants.

The role of excess reactive oxygen species (ROS) with consequent DNA/RNA damage is now recognized as a hallmark of cancer. In JAK2V617F mutated myeloproliferative neoplasms, ROS have been suggested to be important factors in disease initiation and progression. Ruxolitinib is the most widely used drug for myelofibrosis, because it improves symptom-score. However, both the anti-clonal potential and improvement in overall survival are limited. We investigated the impact of ruxolitinib on formation of superoxide radical and hydrogen peroxide by monocytes in sequentially acquired blood samples from patients with myelofibrosis. We also investigated the impact on RNA and DNA damage by measuring urinary excretion of 8-oxo-Guo and 8-oxo-d-Guo. The formation of superoxide by monocytes was reduced significantly during ruxolitinib therapy, but no impact on the formation of hydrogen peroxide by monocytes or the systemic amount of oxidatively damaged RNA or DNA could be demonstrated. We conclude that ruxolitinib holds little anti-oxidative potential.

Aqueous solutions of calf thymus deoxyribonucleic acid (DNA) were exposed to hydrogen peroxide in the presence of air. Base products formed in DNA were identified and quantitated following acid hydrolysis and trimethylsilylation using gas chromatography-mass spectrometry. The yields of these products were dependent upon the hydrogen peroxide concentration, and increased in the following order: 8-hydroxyadenine, cytosine glycol, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 8-hydroxyguanine, thymine glycol, and 4,6-diamino-5-formamidopyrimidine. Previous studies have shown that these compounds are typically formed in DNA in aqueous solution by hydroxyl radicals generated by ionizing radiation. Hydrogen peroxide is thought to participate in a Fenton-like reaction with transition metals, which are readily bound to DNA in trace quantities, resulting in the production of hydroxyl radicals close to the DNA. This proposed mechanism was examined by exposing DNA to hydrogen peroxide either in the presence of a hydroxyl radical scavenger or following pretreatment of DNA with metal-ion chelators. The results indicate that trace quantities of transition metal ions can react readily with hydrogen peroxide to produce radical species. The production of radical species was monitored by determining the altered bases that resulted from the reaction between radicals and DNA. The yields of the base products were reduced by 40 to 60% with 10 mmol dm-3 of dimethyl sulfoxide. A 100-fold increase in the concentration of dimethyl sulfoxide did not result in a further reduction in hydrogen peroxide-induced base damage. DNA which was freed from bound metal ions by pretreatment with metal ion chelators followed by exhaustive dialysis was found to be an ineffective substrate for hydrogen peroxide. The yields of base products measured in this DNA were at background levels. These results support the role of metal ions bound to DNA in the site-specific formation of highly reactive radical species, most likely hydroxyl radicals, in hydrogen peroxide-induced damage to the bases in DNA.

Titanium dioxide (TiO2) is a potential photosensitizer for photodynamic therapy. In this study, the mechanism of DNA damage catalyzed by photo-irradiated TiO2 was examined using [32P]-5'-end-labeled DNA fragments obtained from human genes. Photo-irradiated TiO2 (anatase and rutile) caused DNA cleavage frequently at the guanine residue in the presence of Cu(II) after E. coli formamidopyrimidine-DNA glycosylase treatment, and the thymine residue was also cleaved after piperidine treatment. Catalase, SOD and bathocuproine, a chelator of Cu(I), inhibited the DNA damage, suggesting the involvement of hydrogen peroxide, superoxide and Cu(I). The photocatalytic generation of Cu(I) from Cu(II) was decreased by the addition of SOD. These findings suggest that the inhibitory effect of SOD on DNA damage is due to the inhibition of the reduction of Cu(II) by superoxide. We also measured the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damage, and showed that anatase is more active than rutile. On the other hand, high concentration of anatase caused DNA damage in the absence of Cu(II). Typical free hydroxyl radical scavengers, such as ethanol, mannnitol, sodium formate and DMSO, inhibited the copper-independent DNA photodamage by anatase. In conclusion, photo-irradiated TiO2 particles catalyze the copper-mediated site-specific DNA damage via the formation of hydrogen peroxide rather than that of a free hydroxyl radical. This DNA-damaging mechanism may participate in the phototoxicity of TiO2.

Hydrogen abstraction, in which a radical interacts with another molecule that has a free hydrogen atom (i.e., a hydrogen donor). As a result, the radical binds to the hydrogen atom and becomes stable, whereas the hydrogen donor is converted to a free radical.

Production of acetaldehyde during alcohol metabolism, which through its interactions with proteins and lipids also can lead to radical formation and cell damage. (For information on acetaldehyde and its detrimental effects, see the article in this issue by Tuma and Casey.)

Besides the ROS generation that occurs naturally in the body, humans are constantly exposed to environmental free radicals, including ROS, in the form of radiation, UV light, smog, tobacco smoke, and certain compounds referred to as redox cycling agents, which include some pesticides, but also certain medications used for cancer treatment. The toxicity of these medications against tumor cells (as well as normal body cells) results from the fact that the compounds are modified by cellular enzymes to an unstable intermediate, which then reacts with molecular oxygen to produce the original product plus a superoxide radical. Thus, a vicious cycle of chemical reactions involving these compounds continually produces ROS.

Not all instances of ROS production are detrimental to the organism, however. One beneficial effect, as the main article describes, is the production of ROS by certain immune cells in order to destroy invading foreign organisms (Rosen et al. 1995). Furthermore, recent evidence suggests that ROS, especially hydrogen peroxide, may be important in signal transduction mechanisms in cells and thus may be an integral component of cellular physiology and metabolism (Lander 1997).

Exposure of Escherichia coli to low concentrations of hydrogen peroxide results in DNA damage that causes mutagenesis and kills the bacteria, whereas higher concentrations of peroxide reduce the amount of such damage. Earlier studies indicated that the direct DNA oxidant is a derivative of hydrogen peroxide whose formation is dependent on cell metabolism. The generation of this oxidant depends on the availability of both reducing equivalents and an iron species, which together mediate a Fenton reaction in which ferrous iron reduces hydrogen peroxide to a reactive radical. An in vitro Fenton system was established that generates DNA strand breaks and inactivates bacteriophage and that also reproduces the suppression of DNA damage by high concentrations of peroxide. The direct DNA oxidant both in vivo and in this in vitro system exhibits reactivity unlike that of a free hydroxyl radical and may instead be a ferryl radical. 59ce067264

https://www.therapieloft-fichtelgebirge.de/forum/fernseh-und-filmforum/mia-maleno-taking-shower